Effect of nitrous oxide on halothane-induced hepatotoxicity in hypoxic, enzyme-induced rats

The degree of hepatotoxicity induced by halothane in hypoxic (14% inspired oxygen), enzyme-induced (phenobarbitone treatment for 10 days), male Sprague-Dawley rats was assessed by histological examination and analysis of serum aspartate aminotransferase (Asp. AT) concentrations. There was a significant direct, linear relationship between dose of halothane and histology score (P = 2.96 X 10(-5), and Asp. AT concentration (P = 4.8 X 10(-5) ). The effect of administration of nitrous oxide before (70%) and during (86%) hypoxia was tested for in the presence and absence of 0.75% halothane. Nitrous oxide was found to produce no effect in the absence of halothane, but to potentiate the hepatotoxicity of 0.75% halothane (P = 0.0003 for Asp. AT and 0.0016 for histology scores). The possible mechanisms of this effect are discussed.